Abstract Background Prenatal exposure to persistent organic pollutants (POPs) has been linked to elevated symptoms related to attention deficit hyperactivity disorder (ADHD) in a few studies, but findings remain inconclusive. We aimed to explore how prenatal exposure to POPs affects the developmental course of ADHD symptoms from early childhood to adolescence in the Rhea cohort in Crete, Greece. Methods We determined concentrations of HCB, DDE, and PCBs in first-trimester maternal serum. Child ADHD symptoms were reported by mothers using the ADHD Test at 4 years and the Conners’ Parent Rating Scale at 6, 11 and 15 years. Group-Based Trajectory Modeling was used to classify 551 participants into 4 distinct groups: Stable low (60.1%), Stable high (9.6%), Low-increasing (14.6%), and High-decreasing (15.7%) symptoms. Adjusted multinomial regression models were applied to assess the risk of being grouped into an adverse developmental trajectory as compared to the reference group (stable low), in relation to prenatal POP exposure in 465 children. The analyses were performed in sex-specific manner. Results Prenatal HCB exposure was associated with elevated risk of being grouped in the stable high ADHD symptoms trajectory only in girls (RRR [95%CI]: 2.0 [1.04, 3.82]). Overall, exposure to DDE and sum of PCBs was linked to decreased risk of membership in an adverse ADHD symptoms trajectory. More specifically, in utero exposure to DDE and sum of PCBs was associated with lower risk of being grouped in the low-increasing trajectory for boys (RRR [95%CI]: 0.7 [0.54, 0.95] and 0.5 [0.32, 0.88], respectively) and in the high-decreasing symptoms group for girls (RRR [95%CI]: 0.6 [0.44, 0.84] and 0.5 [0.30, 0.93], respectively). Conclusions The findings suggest that prenatal exposure to HCB is linked to increased risk of stable high ADHD symptoms from preschool age and up to adolescence. The association was pronounced only in girls, a group for which less is understood in relation to ADHD. Key messages • Prenatal exposure to HCB increases the risk of persistently high ADHD symptoms from preschool age to adolescence. • The impact of prenatal HCB exposure on ADHD symptoms is evident in girls.